Heparin-azithromycin microparticles show anti-inflammatory effects and inhibit SARS-CoV-2 and bacterial pathogens associated to lung infections
Anaya, Bryan J and D'Angelo, Davide and Bettini, Ruggero and Molina, Gracia and Sanz, Amadeo and Dea-Ayuela, Maria Auxiliadora and Galiana, Carolina and Rodriguez, Carmina and Tirado, Diego F and Lalatsa, Katerina and Gonzalez-Burgos, Elena and Serrano, Dolores R. (2025) Heparin-azithromycin microparticles show anti-inflammatory effects and inhibit SARS-CoV-2 and bacterial pathogens associated to lung infections. Carbohydrate Polymers, 348. 122930. ISSN 0144-8617 (https://doi.org/10.1016/j.carbpol.2024.122930)
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Abstract
Pulmonary infections are a leading cause of morbidity and mortality worldwide, a situation exacerbated by the COVID-19. Azithromycin (AZM) is used orally to treat pulmonary infections due to its ability to accumulate in lung tissues and immune cells after oral administration. Sulfated polysaccharides, such as heparin, are known to inhibit SARS-CoV-2 entry. This study presents a novel approach focused on developing a dry powder inhaler of AZM-loaded microparticles composed of either heparin or its derivatives. The microparticle formulations exhibited potent antiviral activity against SARS-CoV-2 (IC50 ≤ 95 nM) while retaining superior antibacterial efficacy against Streptococcus pneumoniae and Pseudomonas aeruginosa compared to free AZM (MIC ≤ 15 μg/mL). Importantly, at bactericidal concentrations, no cytotoxic effects were observed on mammalian cells, including Calu-3 cells and red blood cells. The formulations demonstrated effective alveolar aerodynamic deposition (MMAD ranging from 1 μm to 3 μm) with a Fine Particle Fraction below 5 µm close to 50 %. Adopting a conservative estimate of 20 mL for the pulmonary epithelial lining fluid volume in healthy adults, efficacious local concentrations of sulfated polysaccharides and AZM would be delivered to the lung using this multifaceted strategy which holds promise for the treatment of bacterial pulmonary infections associated with COVID-19.
ORCID iDs
Anaya, Bryan J, D'Angelo, Davide, Bettini, Ruggero, Molina, Gracia, Sanz, Amadeo, Dea-Ayuela, Maria Auxiliadora, Galiana, Carolina, Rodriguez, Carmina, Tirado, Diego F, Lalatsa, Katerina ORCID: https://orcid.org/0000-0003-4791-7468, Gonzalez-Burgos, Elena and Serrano, Dolores R.;-
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Item type: Article ID code: 90966 Dates: DateEvent15 January 2025Published28 October 2024Published Online27 October 2024Accepted5 August 2024SubmittedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 28 Oct 2024 16:00 Last modified: 21 Nov 2024 01:25 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/90966